orthomyxovirus, any virus belonging to the family Orthomyxoviridae. Orthomyxoviruses have enveloped virions (virus particles) that measure between 80 and 120 nm (1 nm = 10−9 metre) in diameter. The nucleocapsid, which consists of a protein shell, or capsid, and contains the viral nucleic acids, has helical symmetry.
3. • A22-year old man suddenly experienced
headache, malaise, dry cough and fever.
He basically felt “lousy”. After a couple
of days, he had a sore throat, his cough
had worsened, and he started to feel
nauseated and vomited. Several of his
family members had experienced similar
symptoms during the previous two weeks.
Case Study 3
4. • Influenza virus infections have become such a common
and integral part of our lives that any respiratory infection
that causes discomfort is typically referred to as an
episode of flu.
• In reality, most of these infections are probably not caused
by influenza viruses but by more benign agents.
• True influenza virus infections can pose a serious threat.
• Influenza virus infection in humans occurs in seasonal
epidemics and is estimated to result in up to 5 million
cases of serious disease with 250,000–500,000 deaths.
Introduction 4
6. • Spherical/ filamentous
• Enveloped
• Single, segmented RNA enclosed in a
protein capsid.
• Capsid surrounded by lipoprotein
envelope.
• Two glycoproteins _Neuraminidase and
Haemaggutination are present.
Structure 6
10. HN Terminology 10
• H refers to Haemagglutinnin types and each is
given a number H1, H2 etc
• Neuraminidase is designated N and different
forms are available as well e.g. H5N1 (avian) and
H1N1 (swine).
• Different combinations of H and N
glycoproteins give rise to different strains
11. Haemugglutination 11
• Act with red cells of different species
• Type A and B – RBC's of Fowl, Human
and pigs
• Type C only RBC's of Fowl.
13. Neuraminidase 13
• Neuraminidase are glycoproteins
• Destroys cell receptors by hydrolysis
cleavage.
• There are nine different subtypes
N1 – N9.
14. Two specific proteins used to differentiate among
influenzaA,B and C viruses
➢Matrix protein(M1)
• viral structure protein.
• Interacts with nucleocapsid and envelope.
• Promotes assembly.
➢Membrane protein(M2)
• Forms membrane channel
• Facilitates uncoating and HAproduction.
Specific Proteins 14
15. • Influenza A, B and C the only members.
• Enveloped virion; inactivated by
detergents.
• Segmented negative- sense RNAgenome
with eight nucleocapsid segments.
• Genetic instability responsible for annual
epidemics (mutation:drift) and periodic
pandemics (reassortment:shift).
Characteristics 15
16. • The family Orthomyxoviridae contains three
genera (or types):
• Influenzavirus A, B, and C.
• They are distinguished by their antigenically
distinct nucleoprotein (NP) and matrix (M)
proteins.
• Influenza type A& B are significant human
pathogens influenza while type C is less
important. TypeAinfluenza infect human as well
as animals.
Types 16
17. • Unique feature of this virus lies with antigenic
variation.
• High in typeAvirus
• Less in type B virus
• Not in type C virus
• RNPand matrix protein are stable
• Hemagglutination and Neuraminidase are
independent of the variations.
Antigenic Variation 17
18. • MinorAg changes in HA/NA/both
• Gradual
• Regular intervals
• Mutation in HA/NAgenes
• Epidemics
Antigenic Drift 18
19. • Major changes in HA(2-3), NA(1-3)
• New subtype (unrelated to old virus)
• Unlikely due to mutation.
• Gene assortment (recombination)
• Major epidemics, pandemics.
Antigenic Shift 19
23. • Virions are spherical, between 80nm-120nm
in diameter, helical symmetry, enveloped with
spikes.
• About 80% of the spikes are hemagglutinin
antigen and the remainder are neuraminidase.
There is a layer of matrix protein which
encloses the (-) ss-RNAgenome of the virus.
• RNAis associated with nucleoprotein.
Morphology 23
24. • The genome is composed of eight fragments
complexed with protein to form
ribonucleoprotein arranged in helix.
• Hemagglutinin “HA” is a rod-shaped
glycoprotein with triangular cross section.
• It agglutinates erythrocytes, and plays an
important role in the attachment and entry of
the virus to host cells and in determining
virulence.
• Host cell protease cleaves HAinto two
molecules; HA1 and HA2; a necessary step for
infection.
24
25. • The neuraminidase “NA” is an enzyme which
destroys neuraminic acid “sialic acid”, a
component of the specific cell receptors for the
virus.
• Its main function is in the release of new virus
from cells.
• NAis a glycoprotein, its spikes look like
mushrooms.
• Inside the matrix shell are the nucleoprotein
and an RNAtranscriptase, that is essential for
replication.
25
26. • Endocytosis: engulfment of virion into vacuoles (endosomes),
acidic pH induces a change in the configuration of the HA.
• Uncoating.
• Virus RNAis transported to the cell nucleus
• Transcription by virus RNAtranscriptase to complementary (+)
strand that can function as mRNA
• It also serves as template for the Synthesis of negative RNA
strands for new virions.
• Translation, in host cell cytoplasm, to produce viral proteins.
• The new virions are assembled at the host cell surface
membrane.
• Budding and release
Replication 26
28. Pathogenesis
• Infection is acquired by the respiratory route
causing upper respiratory tract infection.
• Virus multiplies in the epithelium and destroys the
cilia, followed by transient viremia.
• Complications may include
secondary bacterial infection, Reye’s
syndrome
• Reye’s syndrome
• A rare but potentially fatal disease of the liver,
children with fever due to influenza
especially type B should
syndrome.
avoid taking aspirin as this may lead to
Reye's
29. • Incubation period 2-3 days.
• Symptoms may include:
• shivering
• headache
• malaise
• and aching in the limbs and back.
• The temperature rises rapidly to around 39 ºC.
• The severity of influenza is proportional to age.
29
31. • Transmission mainly person to person by
sneezing, coughing or by simply talking.
• Virus likes a cool, less humid atmosphere
(winter heating season).
• Extensively spread by school children.
• The respiratory tract is the gate opening of the
virus.
• Influenza can also be transmitted by saliva,
nasal secretion, feces and blood.
Transmission Of
Influenza virus
31
34. • Immunofluorescence staining of cells in
nasopharyngeal aspirates.
• Virus isolation from throat or nasal swabs,
using chick embryo or cell culture.
• Hemagglutination test or hemagglutination
inhibition.
• Serological testing for specific antibodies.
• RT-PCR
Laboratory Diagnosis 34
35. • Acetaminophen, antihistamines and other drugs
are used to relieve the symptoms.
• Amantadine and rimantadine inhibit an
uncoating step of influenzaAvirus but do not
affect the influenza B and C virus.
• Zanamivir and oseltamivir inhibit bothAand B
as enzyme inhibitor of neuraminidase.
Treatment Of Influenza
virus
35
36. • Avian influenza virus occurs naturally among
birds.
• Wild birds carry viruses in their intestine but
usually do not get sick of them.
• The virus is very contagious among birds and can
make some domesticated birds including chickens,
ducks and turkeys very sick and kill them.
• Infected birds shed the virus in their saliva, nasal
secretions and feces.
Avian influenza Virus
(Bird Flu),H5N1
36
37. • The highly pathogenic form of the virus spreads
more rapidly through flocks of poultry, it may
affect multiple internal organs and has a mortality
rate that can reach % often within 48 hours.
• Infection with H5N1 influenza can occur in
humans.
• Infection results from contact with infected
poultry e.g domesticated chickens, ducks and
turkey.
• Infection from one ill person to another is rare.
Avian influenza Virus
(Bird Flu),H5N1
37
38. • Symptoms in humans have ranged:
• Influenza-like symptoms (fever, cough, sore throat
and muscle aches).
• Eye infections.
• Pneumonia and severe respiratory diseases
• and other life threatening complications
e.g respiratory failure.
• Some virulent influenza strains can escape innate and
adaptive immunity via NS1 protein (nonstructural
protein).
Avian influenza Virus
(Bird Flu),H5N1
38
39. • Elimination of infected birds.
• Careful dealings with birds.
• Restriction of poultry and egg import.
• Administration of antiviral drugs.
• Vaccine is available.
Preventions Of Influenza
Virus
39
42. • Personal hygiene.
• Aeration of living and work places.
• Sneezing and coughing using tissue paper and
disposing it immediately.
• Bed rest of infected persons
• Avoid contact with infected persons.
• Antiviral drugs (e.g Neuraminidase inhibitors)
• Vaccine is available.
Control 42